Project Summary/Abstract A diverse array of pharmaceutical treatments has been reported to successfully rescue, or partially rescue, learning and memory deficits in the Down syndrome mouse model Ts65Dn. These advances have led to calls for a more robust national translational research agenda for DS. However, the evaluation of the efficacy of targeted treatments for DS has been hampered by a lack of outcome measures that have been validated for DS. The need for validated outcome measures for DS is particularly acute for the earliest years of life because, presumably, interventions that begin early have the greatest potential to create a cascade of positive events that can have cumulative, pervasive, long-lasing benefits. Unfortunately, such measures are virtually nonexistent prior to the school-age years. In the present project, we propose to evaluate the feasibility and psychometric properties of a variety of prelinguistic and spoken language metrics collected in naturalistic contexts, which have been used in research and clinical practice to track developmental improvements in a number of populations of children, for use in treatment studies focused on young with DS. The focus on language and communication as endpoints for treatment studies of DS is particularly attractive given that difficulties in these domains are among the most salient features of the DS phenotype. In this project, we propose to (1) evaluate the psychometric properties of five metrics of prelinguistic communication skills, (2) evaluate the psychometric properties of four metrics of early spoken language skills, and (3) characterize the developmental trajectories of these various metrics of prelinguistic and spoken language in young children with DS through cross-sectional approaches. These aims will be addressed by collecting two naturalistic communication samples from children with DS aged 2.50-7.99 years: Early Social Communication Scales (ESCS) and a semi-structured play session with an examiner. Measures derived from the samples will include those indexing prelinguistic communication (e.g., ESCS Initiating Joint Attention, Initiating Behavioral Requests, and Initiating Social Interaction scores; Communication Complexity Scale score; Expressive Communication Index-Weighted Communication score) and spoken language (e.g., talkativeness, lexical diversity, syntactic complexity, intelligibility). Test-retest reliability will be assessed over 2 weeks (+/-3 days). Standardized measures will be used as indicators of construct validity. A 1-year longitudinal follow-up will yield an estimate of relative sensitivity to change of the various measures. Feasibility of multiple-site implementation will be evaluated by comparing samples across sites on key psychometric indicators. The developmental trajectories of these metrics will be explored by describing performance as a function of subject characteristics (e.g., chronological age, nonverbal cognition, and verbal cognition).